Gastrointestinal hormones and the regulation of β-cell mass

Jeremy Arlin Lavine, Alan D. Attie*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Type 2 diabetes occurs due to a relative deficit in β-cell mass or function. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), and gastrin are gastrointestinal hormones that are secreted in response to nutrient intake, regulating digestion, insulin secretion, satiety, and β-cell mass. In this review, we focus upon β-cell mass regulation. β-cell mass expands through β-cell proliferation and islet neogenesis; β-cell mass is lost via apoptosis. GLP-1 and GIP are well-studied gastrointestinal hormones and influence β-cell proliferation, apoptosis, and islet neogenesis. CCK regulates β-cell apoptosis and mitogenesis, and gastrin stimulates islet neogenesis. GLP-1 and GIP bind to G protein-coupled receptors and regulate β-cell mass via multiple signaling pathways. The protein kinase A pathway is central to this process because it directly regulates proliferative and anti-apoptotic genes and transactivates several signaling cascades, including Akt and mitogen-activated protein kinases. However, the signaling pathways downstream of G protein-coupled CCK receptors that influence β-cell mass remain unidentified. Gastrointestinal hormones integrate nutrient signals from the gut to the β-cell, regulating insulin secretion and β-cell mass adaptation.

Original languageEnglish (US)
Pages (from-to)41-58
Number of pages18
JournalAnnals of the New York Academy of Sciences
Volume1212
DOIs
StatePublished - Nov 2010

Keywords

  • CCK
  • GIP
  • GLP-1
  • Gastrin
  • Islet
  • Protein kinase B/Akt
  • β-cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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